Sterically controlled syntheses of optically active organic compounds. XV. Synthesis of optically active aspartic acid through .beta.-lactam

Abstract

Optically active iV-alkyl-A-chloroacetamidoacetonitriles were prepared and were converted to their corresponding /3-lactams by treatment with sodium hydride. The /3-lactams were hydrolyzed and hydrogenolyzed to form optically active aspartic acid. When (R )-a-alkylbenzylamines were used, (S)-aspartic acid was the result. The yield of aspartic acid from aminoacetonitriles ranged from 36 to 96%. The optical purity of aspartic acid ranged from 21 to 67%. A temperature effect on the sterically controlled reaction was examined.The effect of temperature on the optical purity and yield was found to be small. To examine whether the sterically controlled reaction is due to an asymmetric induction or to a first-order asymmetric transformation, equilibration reactions were carried out using three solvents (dioxane, benzene, acetonitrile). The results indicate that the formation of optically active aspartic acid is largely due to an asymmetric induction.

The synthesis of alkyl aryl nitriles from N-(1-arylalkylidene)cyanomethyl amines: some mechanistic conclusions

“…)benzylformimidoyl cyanide 4c. Starting from N-(α-methyl)benzylaminoacetonitrile (1.0 g, 6.3 mmol), 18 a mixture of 4c, starting amine and 1c was obtained in an 88 : 10 : 2 ratio, respectively (0.65 g; not distilled). 4c, E isomer: 1 H NMR (CDCl 3 ) δ: 1.59 (d, 3H, CH 3 , J 6.6 Hz), 4.59 (q, 1H, CH, J 6.6 Hz), 7.29-7.39 (m, Ph and N᎐ ᎐ CH); traces of the Z isomer were also detected.…”

“…The product was recrystallised from n-pentane-diethyl ether (95 : 5 v/v). (11), 177 (100), 152 (8), 150 (11), 139 (18), 137 (55), 102 (12), 75 (12).…”

“…N-( -Methyl)benzylaminoacetonitrile. 18 Starting from 5 g (41.3 mmol) of (α-methyl)benzylamine, 2.5 g was obtained (38%; bp 86-88 ЊC, 0.2 mmHg). 1 H NMR (CDCl 3 ) δ: 1.41 (d, 3H, CH 3 , J 7.8 Hz), 2.4 (br s, 1H, NH), 3.42 (dd, 2H, CH 2 CN, J 17 Hz), 4.09 (q, 1H, CH, J 7.8 Hz), 7.28-7.38 (m, 5H, Ph); mass spectrum (70 eV) m/z (relative intensity): 158 (M ϩ , 6), 116 (20), 106 (10), 105 (100), 103 (12), 79 (12), 77 (21), 51 (9); IR (CCl 4 ): ν/cm Ϫ1 2235 (CN), 3334 (NH).…”

“…Yield = 90%. 1 H NMR (CDCl 3 ) δ: 7.16-7.86 (m, 10H, aromatic), 4.22 (t, 1H, J 6.6 Hz, CH), 2.08-1.76 (m, 2H), 1.52-1.20 (m, 4H), 0.89 (t, 3H, J 7.5 Hz); mass spectrum (70 eV) m/z (relative intensity): 276 (M ϩ , 34), 275 (92), 233 (12), 222 (12), 220 (24), 219 (80), 209 (18), 208 (100), 194 (11), 165 (37), 117 (10), 116 (93), 104 (34), 103 (13), 89 (14), 77 (32).…”

Iridium-Catalyzed Single-Step N-Substituted Lactam Synthesis from Lactones and Amines

“…5 Moreover, the intramolecular cyclization of haloamides with Brønsted bases affords lactams. 6 Among these methods, the lactamization of lactones with amines is a straightforward approach because the substrates are readily available without any prefunctionalization. However, the previous methods for this reaction suffer from harsh temperatures (220−270 °C) or high pressures 7 and require stoichiometric amounts of activating reagents 8 and multistep reactions.…”